title: Junk DNA and sectorial gene repression.
abstract: Transcriptional repression in eukaryotes often involves tens or hundreds of kilobase pairs, two to three orders of magnitude more than the bacterial operator/repressor model does. Classical repression, represented by this model, was maintained over the whole span of evolution under different guises, and consists of repressor factors interacting primarily with promoters and, in later evolution, also with enhancers. The use of much larger amounts of DNA in the other mode of repression, here called the sectorial mode ('superrepression'), results in the conceptual transfer of so-called junk DNA to the domain of functional DNA. This contribution to the solution of the c-value paradox involves perhaps 15% of genomic 'junk,' and encompasses the bulk of the introns, thought to fill a stabilizing role in sectorially repressed chromatin structures. In the case of developmental genes, such structures appear to be heterochromatoid in character. However, solid clues regarding general structural features of superrepressed terminal differentiation genes remain elusive. The competition among superrepressible DNA sectors for sectorially binding factors offers, in principle, a molecular mechanism for developmental switches. Position effect variegation may be considered an abnormal manifestation of normal processes that underly development and involve heterochromatoid sectorial repression, which is apparently required for local elimination or modulation of morphological features (morpholysis). Sectorial repression of genes participating either in development or in terminal differentiation is considered instrumental in establishing stable cell types, and provides a basis for the distinction between determination and cell type specification. The gamut of possible stable cell types may have been broadened by the appearance in evolution of heavy isochores. Additional types of relatively frequent GC-rich cis-acting DNA motifs may offer reiterated binding sites to factors endowed with a selective (though not individually strong) affinity for these motifs. The majority of sequence motifs thought to be used in superrepression need not be individually maintained by natural selection. It is re-emphasized that the dispensability of sequences is not an indicator of their nonfunctionality and that in many cases, along noncoding sequences, nucleotides tend to fill functions collectively, rather than individually.
authors.affiliation: Institute of Molecular Medical Sciences, Palo Alto, CA 94306, USA.
authors.forename: E
authors.initials: E
authors.lastname: Zuckerkandl
mesh_terms: D000818:Animals; D004247:DNA / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D006570:Heterochromatin; D004247:DNA